Citrulline as a biomarker of bacteraemia during induction treatment for childhood acute lymphoblastic leukaemia.
Adolescent
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Bacteremia
/ blood
Bacteria
/ isolation & purification
Biomarkers
/ blood
Child
Child, Preschool
Citrulline
/ blood
Doxorubicin
/ administration & dosage
Female
Follow-Up Studies
Humans
Induction Chemotherapy
Infant
Male
Methotrexate
/ administration & dosage
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ drug therapy
Prognosis
Prospective Studies
Retrospective Studies
Vincristine
/ administration & dosage
acute lymphoblastic leukaemia
bacteraemia
citrulline
mucositis
neutropaenia
Journal
Pediatric blood & cancer
ISSN: 1545-5017
Titre abrégé: Pediatr Blood Cancer
Pays: United States
ID NLM: 101186624
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
16
08
2020
revised:
20
10
2020
accepted:
21
10
2020
pubmed:
7
11
2020
medline:
28
4
2021
entrez:
6
11
2020
Statut:
ppublish
Résumé
Systemic infections are a major cause of morbidity in children with acute lymphoblastic leukaemia (ALL). However, identification of patients at increased risk is still a challenge. Knowing that both neutropaenia and gastrointestinal toxicity are risk factors for bacteraemia, we aimed at comparing absolute neutrophil counts (ANC) and plasma citrulline levels (indicating enterocyte loss) in children with ALL with and without bacteraemia during induction treatment. We prospectively included 61 children with ALL treated according to the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL-2008 protocol. ANC and plasma C-reactive protein (CRP) were measured on treatment days 1, 8, 15, 22 and 29. Plasma citrulline was measured on days 1, 8, 15 and 29. Bacteraemia episodes during induction treatment were recorded retrospectively. Nineteen of sixty-one (31%) patients experienced bacteraemia occurring on median day 13 (range 5-20). Patients with bacteraemia during induction treatment had lower citrulline level on day 15 (P < .01) compared to patients without bacteraemia, indicating more severe enterocyte loss. Nevertheless, ANC was similar in the two patient groups on days 8 and 15. CRP was negatively correlated with same-day citrulline (P < .03 for all) and ANC (P < .04 for all). During chemotherapy-induced neutropaenia, plasma citrulline may help identify patients at increased risk of bacteraemia.
Sections du résumé
BACKGROUND
Systemic infections are a major cause of morbidity in children with acute lymphoblastic leukaemia (ALL). However, identification of patients at increased risk is still a challenge. Knowing that both neutropaenia and gastrointestinal toxicity are risk factors for bacteraemia, we aimed at comparing absolute neutrophil counts (ANC) and plasma citrulline levels (indicating enterocyte loss) in children with ALL with and without bacteraemia during induction treatment.
PROCEDURE
We prospectively included 61 children with ALL treated according to the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL-2008 protocol. ANC and plasma C-reactive protein (CRP) were measured on treatment days 1, 8, 15, 22 and 29. Plasma citrulline was measured on days 1, 8, 15 and 29. Bacteraemia episodes during induction treatment were recorded retrospectively.
RESULTS
Nineteen of sixty-one (31%) patients experienced bacteraemia occurring on median day 13 (range 5-20). Patients with bacteraemia during induction treatment had lower citrulline level on day 15 (P < .01) compared to patients without bacteraemia, indicating more severe enterocyte loss. Nevertheless, ANC was similar in the two patient groups on days 8 and 15. CRP was negatively correlated with same-day citrulline (P < .03 for all) and ANC (P < .04 for all).
CONCLUSIONS
During chemotherapy-induced neutropaenia, plasma citrulline may help identify patients at increased risk of bacteraemia.
Substances chimiques
Biomarkers
0
Citrulline
29VT07BGDA
Vincristine
5J49Q6B70F
Doxorubicin
80168379AG
Methotrexate
YL5FZ2Y5U1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e28793Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2020 Wiley Periodicals LLC.
Références
O'Connor D, Bate J, Wade R, et al. Infection-related mortality in children with acute lymphoblastic leukemia: an analysis of infectious deaths on UKALL2003. Blood. 2014;124(7):1056-1061.
Christensen MS, Heyman M, Möttönen M, Zeller B, Jonmundsson G, Hasle H. Treatment-related death in childhood acute lymphoblastic leukaemia in the Nordic countries: 1992-2001. Br J Haematol. 2005;131(1):50-58.
Inaba H, Pei D, Wolf J, et al. Infection-related complications during treatment for childhood acute lymphoblastic leukemia. Ann Oncol. 2017;28(2):386-392.
Lehrnbecher T, Robinson P, Fisher B, et al. Guideline for the management of fever and neutropenia in children with cancer and hematopoietic stem-cell transplantation recipients: 2017 update. J Clin Oncol. 2017;35(18):2082-2094.
Bate J, Gibson F, Johnson E, et al. Neutropenic sepsis: prevention and management of neutropenic sepsis in cancer patients (NICE Clinical Guideline CG151). Arch Dis Child Educ Pract. 2013;98(2):73-75.
Hann I, Viscoli C, Paesmans M, Gaya H, Glauser M. A comparison of outcome from febrile neutropenic episodes in children compared with adults: results from four EORTC studies. Br J Haematol. 1997;99(3):580-588.
Hakim H, Flynn PM, Knapp KM, Srivastava DK, Gaur AH. Etiology and clinical course of febrile neutropenia in children with cancer. J Pediatr Hematol Oncol. 2009;31(9):623-629.
Miedema KGE, Tissing WJE, Abbink FCH, et al. Risk-adapted approach for fever and neutropenia in paediatric cancer patients-a national multicentre study. Eur J Cancer. 2016;53:16-24.
Ammann RA, Hirt A, Lüthy AR, Aebi C. Identification of children presenting with fever in chemotherapy-induced neutropenia at low risk for severe bacterial infection. Med Pediatr Oncol. 2003;41(5):436-443.
Castagnola E, Fontana V, Caviglia I, et al. A prospective study on the epidemiology of febrile episodes during chemotherapy-induced neutropenia in children with cancer or after hemopoietic stem cell transplantation. Clin Infect Dis. 2007;45(10):1296-1304.
El-Mahallawy HA, El-Wakil M, Moneer MM, Shalaby L. Antibiotic resistance is associated with longer bacteremic episodes and worse outcome in febrile neutropenic children with cancer. Pediatr Blood Cancer. 2011;57(2):283-288.
Kamboj M, Sepkowitz KA. Nosocomial infections in patients with cancer. Lancet Oncol. 2009;10(6):589-597.
van Vliet MJ, Harmsen HJM, de Bont ESJM, Tissing WJE. The role of intestinal microbiota in the development and severity of chemotherapy-induced mucositis. PLoS Pathog. 2010;6(5):e1000879.
Kuiken NSS, Rings EHHM, Tissing WJE. Risk analysis, diagnosis and management of gastrointestinal mucositis in pediatric cancer patients. Crit Rev Oncol Hematol. 2015;94(1):87-97.
Elting LS, Cooksley C, Chambers M, Cantor SB, Manzullo E, Rubenstein EB. The burdens of cancer therapy: clinical and economic outcomes of chemotherapy-induced mucositis. Cancer. 2003;98(7):1531-1539.
Vera-Llonch M, Oster G, Ford CM, Lu J, Sonis S. Oral mucositis and outcomes of allogeneic hematopoietic stem-cell transplantation in patients with hematologic malignancies. Support Care Cancer. 2007;15(5):491-496.
Villa A, Sonis ST. Mucositis. Pathobiology and management. Curr Opin Oncol. 2015;27(3):159-164.
Rathe M, Sorensen GL, Wehner PS, et al. Chemotherapeutic treatment reduces circulating levels of surfactant protein-D in children with acute lymphoblastic leukemia. Pediatr Blood Cancer. 2017;64(3):1-8.
Herbers AH, Feuth T, Donnelly JP, Blijlevens NM. Citrulline-based assessment score: first choice for measuring and monitoring intestinal failure after high-dose chemotherapy. Ann Oncol. 2010;21(8):1706-1711.
Bahri S, Zerrouk N, Aussel C, et al. Citrulline: from metabolism to therapeutic use. Nutrition. 2013;29(3):479-484.
Rathe M, De Pietri S, Wehner PS, et al. Bovine colostrum against chemotherapy-induced gastrointestinal toxicity in children with acute lymphoblastic leukemia: a randomized, double-blind, placebo-controlled trial. J Parenter Enteral Nutr. 2020;44(2):337-347.
Toft N, Birgens H, Abrahamsson J, et al. Risk group assignment differs for children and adults 1-45 yr with acute lymphoblastic leukemia treated by the NOPHO ALL-2008 protocol. Eur J Haematol. 2013;90(5):404-412.
Peake RWA, Law T, Hoover PN, Gaewsky L, Shkreta A, Kellogg MD. Improved separation and analysis of plasma amino acids by modification of the MassTrak™ AAA Solution Ultraperformance® liquid chromatography method. Clin Chim Acta. 2013;423:75-82.
U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE). Version 4.0. https://www.eortc.be/services/doc/ctc/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf. Accessed October 30, 2020.
Lausen B, Schmiegelow K, Andreassen B, Madsen HO, Garred P. Infections during induction therapy of childhood acute lymphoblastic leukemia - No association to mannose-binding lectin deficiency. Eur J Haematol. 2006;76(6):481-487.
Bergmann K, Hasle H, Asdahl P, et al. Central venous catheters and bloodstream infection during induction therapy in children with acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2016;38(3):e82-e87.
Pui C-H, Campana D, Pei D, et al. Treating childhood acute lymphoblastic leukemia without cranial irradiation. N Engl J Med. 2009;360(26):2730-2741.
Rungoe C, Malchau EL, Larsen LN, Schroeder H. Infections during induction therapy for children with acute lymphoblastic leukemia. The role of sulfamethoxazole-trimethoprim (SMX-TMP) prophylaxis. Pediatr Blood Cancer. 2010;55(2):304-308.
Sulis ML, Blonquist TM, Stevenson KE, et al. Effectiveness of antibacterial prophylaxis during induction chemotherapy in children with acute lymphoblastic leukemia. Pediatr Blood Cancer. 2018;65(5):1-8.
Herbers AHE, de Haan AFJ, van der Velden WJFM, Donnelly JP, Blijlevens NMA. Mucositis not neutropenia determines bacteremia among hematopoietic stem cell transplant recipients. Transpl Infect Dis. 2014;16(2):279-285.
Herbers AHE, Blijlevens NMA, Donnelly JP, de Witte TJM. Bacteraemia coincides with low citrulline concentrations after high-dose melphalan in autologous HSCT recipients. Bone Marrow Transplant. 2008;42(5):345-349.
van der Velden WJFM, Blijlevens NMA, Feuth T, Donnelly JP. Febrile mucositis in haematopoietic SCT recipients. Bone Marrow Transplant. 2009;43(1):55-60.
van der Velden WJFM, Herbers AHE, Feuth T, Schaap NPM, Donnelly JP, Blijlevens NMA. Intestinal damage determines the inflammatory response and early complications in patients receiving conditioning for a stem cell transplantation. PLoS One. 2010;5(12):e15156.
Bodey GP, Buckley M, Sathe YS, Freireich EJ. Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann Intern Med. 1966;64(2):328-340.
Schimpff S, Satterlee W, Young VM, Serpick A. Empiric therapy with carbenicillin and gentamicin for febrile patients with cancer and granulocytopenia. N Engl J Med. 1971;284(19):1061-1065.
Lappalainen M, Jokkala J, Juutilainen A, et al. Novel biomarker candidates for febrile neutropenia in hematological patients using nontargeted metabolomics. Dis Markers. 2018;2018:6964529.
Celebi S, Sezgin ME, Cakır D, et al. Catheter-associated bloodstream infections in pediatric hematology-oncology patients. Pediatr Hematol Oncol. 2013;30(3):187-194.
Zakhour R, Hachem R, Alawami HM, et al. Comparing catheter-related bloodstream infections in pediatric and adult cancer patients. Pediatr Blood Cancer. 2017;64(10):e26537.
Kelly MS, Conway M, Wirth KE, Potter-Bynoe G, Billett AL, Sandora TJ. Microbiology and risk factors for central line-associated bloodstream infections among pediatric oncology outpatients. J Pediatr Hematol Oncol. 2013;35(2):e71-e76.
Costa SF, Miceli MH, Anaissie EJ. Mucosa or skin as source of coagulase-negative staphylococcal bacteraemia? Lancet Infect Dis. 2004;4(5):278-286.
Blijlevens NMA, Van t Land B, Ii Donnelly J, De Pauw BE. Gram-positive bacteremia coincides with impaired gut integrity in HSCT recipients. Int J Infect Dis. 2002;6:2S32-2S33.
Costa SF, Barone AA, Miceli MH, et al. Colonization and molecular epidemiology of coagulase-negative staphylococcal bacteremia in cancer patients: a pilot study. Am J Infect Control. 2006;34(1):36-40.
Sonis ST. The pathobiology of mucositis. Nat Rev Cancer. 2004;4(4):277-284.
Kornblit B, Müller K. Sensing danger: toll-like receptors and outcome in allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2017;52(4):499-505.
van der Velden WJFM, Herbers AHE, Netea MG, Blijlevens NMA. Mucosal barrier injury, fever and infection in neutropenic patients with cancer: introducing the paradigm febrile mucositis. Br J Haematol. 2014;167(4):441-452.
Blijlevens NM, Donnelly JP, De Pauw BE. Mucosal barrier injury: biology, pathology, clinical counterparts and consequences of intensive treatment for haematological malignancy: an overview. Bone Marrow Transplant. 2000;25(12):1269-1278.